The present invention provides a novel process for preparing known compounds. This invention also provides novel intermediates to be used in this process. More particularly, the present invention provides a novel process for preparing prostaglandins from D-glucose, and novel intermediates to be used therein.
The prostaglandins are a family of compounds which are derivatives of prostanoic acid. (See, e.g., Bergstrom, et al., Pharmacol. Rev. 20:1 (1968), and references cited therein.) A trivial system of nomenclature has been divised for this class of compounds, see, N. A. Nelson, Journal of Medicinal Chemistry, 17:911 (1974). This system of nomenclature is used below.
The prostaglandins are known to be useful for a wide variety of pharmaceutical purposes including decreasing blood pressure, stimulating smooth muscles, inhibiting gastric secretion, controlling spasms and facilitating breathing in asthmatic conditions, decongesting nasal passages, decreasing blood platelet adhesion and inhibiting blood platelet aggregation and thrombis formation, and a variety of uses in the reproductive area including labor induction, abortion, cervical dilatation, estrus regulation, and menstrual regulation. For a recent discussion of prostaglandins which are currently being developed commercially, see N. A. Nelson, et al., Chemical and Engineering News, pp. 30-44 (Aug. 16, 1982).
9-Deoxy-9-methylene-PGE-type compounds are disclosed in U.S. Pat. No. 4,060,534. 9-Deoxo-9-methylene-16,16-dimethyl-prostaglandin E2 (formula I), has been given the generic name meteneprost. This prostaglandin is useful in the reproductive area; more particularly, it is useful for menses induction and cervical dilatation. The prior art process set forth in the '534 patent cited above produces meteneprost from the cyclopentane-lactone compound of the formula II using a 14 step sequence. This cyclopentane-lactone compound is itself prepared by a 9 step sequence from norbornadiene. The final product produced by this process is contaminated by varying amounts of the corresponding 5,6-trans isomer, the separation of which requires an exceedingly difficult and laborous chromaographic process. Thus, this process is not satisfactory for large scale commercial production of this material.